Lipid peroxidation occurring as a consequence of injuries is a secondary process. Some cells are immediately destroyed when the tissues are damaged. During the next hours the injury is extended to the surrounding cells. This is induced by free oxygen radicals which attack the lipid layer of the cellular membrane and may eventually lead to cell death by damaging the membrane and releasing hydrogen peroxide. Compounds inhibiting lipid peroxidation can prevent this secondary process occurring as sequels of e.g. paralyses, cephalic or spinal traumas. Compounds possessing such an effect may be utilized e.g. for the treatment of Alzheimer's disease, muscular dystrophy and the like.
The following publications discussing the preparation of piperazinylpyrimidine derivatives are known; the preparation of antiinflammatory 2,4-diamino-6-piperazinylpyrimidine derivatives is described in the GB patent specification No. 1,345,640. In the target compounds the amino groups, being the same or different, may be monoalkylamino groups containing 1 to 6 carbon atoms, cycloalkylamino groups containing at most 6 carbon atoms or a morpholino group whereas the amino group in position 4 may be a piperazino group, too.
According to this patent specification the starting substance of the synthesis is 2,4,6-trichloropyrimidine of the formula (IV) (see hereinafter) which is first reacted with morpholine, then the dichloro compound obtained is brought into reaction with ethylamine, finally the monochloro compound formed is reacted with piperazine to give 4-ethylamino-2-morpholino-6-(1-piperazinyl)pyrimidine as described in the examples. Compounds containing a morpholino group as one of the two amino groups and a cycloalkylamino or monoalkylamino group containing at most 4 carbon atoms are indicated to be most effective. Among these in the preferred compounds one of the two amino groups is ethylamino or cyclopropylamino group, the other one is a morpholino group. Detailed examples with physical characteristics are given for the preparation of 2-ethylamino-4-morpholino-6-(1-piperazinyl)pyrimidine and 4-cyclopropylamino-2-morpholino-6-(1-piperazinyl)pyrimidine, too.
In the published German patent specification No. 2,630,140 2,4-diaminopyrimidine derivatives are described, wherein the amino groups are mono- or disubstituted; the substituents may be C.sub.1-4 alkyl, C.sub.2-4 alkenyl or cyclopropyl groups. A post-emergent herbicidal activity is attributed to these compounds.
The synthesis of [piperazinyl-bis(amino)pyrimidinyl]-steroids of primarily lipid peroxidation-inhibiting activity is described in the published PCT patent application No. WO 87/01706. There are given examples for the preparation of piperazinyl-bis(alkylamino)pyrimidine derivatives used as starting substances for the steroid derivatives mentioned above, too. Thus, 2,4,6-trichloropyrimidine is reacted primarily with saturated or unsaturated amines containing 1 to 3 carbon atoms as well as pyrrolidine, morpholine, hexamethyleneimine or N-methylpiperazine. According to the biological data published in this application, 4-(1-piperazinyl)-2,6-bis(pyrrolidino)pyrimidine proved to be the most favourable one for the preparation of lipid peroxidation-inhibiting compounds.
It is known from the published PCT patent application No. WO P 91/11453 that the strength of the lipid peroxidation-inhibiting effect is significantly influenced by using some-piperazinyl-bis(alkylamino)pyrimidine derivatives as substituents connected e.g. to compounds having steroid skeleton or other substances having a similar structure.